US2010286027A1PendingUtilityA1

Anti-bacterial compositions

45
Assignee: NOVARTIS AGPriority: Jan 15, 2008Filed: Jan 13, 2009Published: Nov 11, 2010
Est. expiryJan 15, 2028(~1.5 yrs left)· nominal 20-yr term from priority
Inventors:Scott J. ParkinsonLaurent Perez
A61P 31/00A61P 31/04A61P 1/00A61K 38/00C07K 14/435Y02A50/30
45
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Claims

Abstract

The invention relates to an isolated protein for use as an antimicrobial agent comprises a plurality of LRR (leucine rich repeat) domains, each LRR domain independently comprising an amino acid sequence of formula (I): (F1LxxLxL(xxZ) Y F2) wherein: F1 and F2 are independently, a contiguous amino acid sequence of between 1 and 30 residues; x can be any amino acid; L can be Leu, Ile, Val or Phe; Z can be NxL or CxxL; N is Asn, Thr, Ser or Cys; C is Cys or Ser; and Y=0 or 1.

Claims

exact text as granted — not AI-modified
1 . An isolated protein comprising a plurality of LRR (leucine rich repeat) domains, for use as an antimicrobial agent. 
     
     
         2 . The protein of  claim 1 , wherein the C-terminus of the protein is an LRR domain. 
     
     
         3 . The protein of  claim 1 , wherein each LRR domain independently consists essentially of an amino acid sequence of formula (I):
   (F1LxxLxL(xxZ) Y F2)  (I)   wherein:   F1 and F2 are independently, a contiguous amino acid sequence of between 1 and 30 residues;   x can be any amino acid;   L can be Leu, Ile, Val or Phe;   Z can be NxL or CxxL;   N is Asn, Thr, Ser or Cys;   C is Cys or Ser; and   Y=0 or 1.   
     
     
         4 . The protein of  claim 3 , wherein at least 2 L residues in each LRR are Leu. 
     
     
         5 . The protein of  claim 4 , wherein at least 3 L residues in each LRR are Leu. 
     
     
         6 . The protein of  claim 1 , comprising at least 3 LRR domains. 
     
     
         7 . The protein of  claim 1 , comprising at least 4 LRR domains. 
     
     
         8 . The protein of  claim 1 , comprising at least 5 LRR domains. 
     
     
         9 . The protein of  claim 1 , comprising at least 6 LRR domains. 
     
     
         10 . The protein of  claim 1 , wherein the protein is antibacterial. 
     
     
         11 . The protein of  claim 10 , for use on gram positive bacteria. 
     
     
         12 . The protein of  claim 10  for use on gram negative bacteria. 
     
     
         13 . The protein of  claim 10 , for treatment of bacterial infection in a human. 
     
     
         14 . The protein of  claim 1 , which is selected from the group consisting of NOD, TLR, CIITA. 
     
     
         15 . The protein of  claim 14 , wherein the NOD is NOD1 or NOD2. 
     
     
         16 . The protein of  claim 14 , wherein the TLR is selected from the group consisting of; TLR1, TLR2, TLR3, TLR4, TLR5TLR6, TLR7, TLR8, TLR9, TLR10, TLR11, TLR12, TLR13. 
     
     
         17 . The protein of  claim 16 , wherein the TLR is TLR2, TLR4 or TLR5. 
     
     
         18 . The protein of  claim 1 , wherein the protein has direct antimicrobial activity per se. 
     
     
         19 . The protein of  claim 18 , wherein the direct antimicrobial activity is effective under in vitro conditions. 
     
     
         20 . The protein of  claim 1 , comprising 5 or more LRR (leucine rich repeat) domains, for use as an antibacterial agent, wherein the C-terminus of the protein is an LRR domain and each LRR domain independently comprises an amino acid sequence of formula (I):
   (F1LxxLxL(xxZ) Y F2)  (I)   wherein:   F1 and F2 are independently, a contiguous amino acid sequence of between 1 and 30 residues;   x can be any amino acid;   L can be Leu, Ile, Val or Phe;   Z can be NxL or CxxL;   N is Asn, Thr, Ser or Cys;   C is Cys or Ser; and   Y=0 or 1.   
     
     
         21 . The protein of  claim 20 , wherein at least 2 L residues in each LRR are Leu. 
     
     
         22 . A pharmaceutical composition comprising an isolated protein according to  claim 1 . 
     
     
         23 . The pharmaceutical composition of  claim 20 , for use as an antimicrobial. 
     
     
         24 . The pharmaceutical composition of  claim 22 , for use in treating and/or preventing bacterial infection in a host susceptible to infection. 
     
     
         25 . The composition of  claim 24  wherein the host is a mammal such as human. 
     
     
         26 . The composition of  claim 24 , wherein the human is afflicted with a gastrointestinal disease such as Crohns disease, IBD or IBS. 
     
     
         27 . A method of treating a microbial infection in a human comprising administering to that human an effective amount of an isolated protein comprising a plurality of LRR (leucine rich repeat) domains. 
     
     
         28 . The method of  claim 27 , wherein the C-terminus of the protein is an LRR domain. 
     
     
         29 . The method of  claim 27 , wherein each LRR domain independently consists essentially of an amino acid sequence of formula (I):
   (F1LxxLxL(xxZ) Y F2)  (I)   wherein:   F1 and F2 are independently, a contiguous amino acid sequence of between 1 and 30 residues;   x can be any amino acid;   L can be Leu, Ile, Val or Phe;   Z can be NxL or CxxL;   N is Asn, Thr, Ser or Cys;   C is Cys or Ser; and   Y=0 or 1.   
     
     
         30 . The method of  claim 29 , wherein at least 2 L residues in each LRR are Leu. 
     
     
         31 . The method of  claim 29 , wherein at least 3 L residues in each LRR are Leu. 
     
     
         32 . The method of  claim 27 , wherein the protein comprises at least 3 LRR domains. 
     
     
         33 . The method of  claim 27 , wherein the protein comprises at least 4 LRR domains. 
     
     
         34 . The method of  claim 27 , wherein the protein comprises at least 5 LRR domains. 
     
     
         35 . The method of  claim 27 , wherein the protein comprises at least 6 LRR domains.

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